Department of Pediatrics, The University of Chicago , Chicago, Illinois, USA.
Division of Molecular and Cardiovascular Biology, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio, USA.
Nucleus. 2020 Dec;11(1):299-314. doi: 10.1080/19491034.2020.1832734.
Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins' function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins' function in the nuclear interior.
几十年来的研究已经证实，核层蛋白聚合物形成核层，这是一种支持核膜结构并将异染色质固定在核周的蛋白质网格。对于核内部未聚合的核层蛋白知之甚少，现在已知其中一些会发生特定的磷酸化。最近的一项发现表明，磷酸化的核层蛋白与基因增强子区域结合，这为一个新的假设提供了依据，即核层蛋白磷酸化可能影响核内部的转录调控。在这篇综述中，我们讨论了磷酸化核层蛋白的调节、定位和功能。我们总结了在各种生物学背景下磷酸化核层蛋白的激酶。我们的讨论扩展到了核层蛋白病，这是一系列由核层蛋白基因突变引起的退行性疾病，如心肌病和早衰症。我们比较了基于核层蛋白在核层中的功能的核层蛋白病发病机制的主流假设，以及基于核内部磷酸化核层蛋白功能的新兴假设。
